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Blood, Vol. 92 No. 7 (October 1), 1998: pp. 2556-2570

Nonobese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) Mouse as a Model System to Study the Engraftment and Mobilization of Human Peripheral Blood Stem Cells

Johannes C.M. van der Loo, Helmut Hanenberg, Ryan J. Cooper, F.-Y. Luo, Emmanuel N. Lazaridis, and David A. Williams

From the Department of Pediatrics, Section of Hematology/Oncology, Herman B Wells Center for Pediatric Research, the Stem Cell Laboratory, Cancer Research Building, and the Division of Biostatistics, Regenstrief Institute for Health Care, Indiana University School of Medicine, Indianapolis, IN; and Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, IN.

Mobilized CD34+ cells from human peripheral blood (PB) are increasingly used for hematopoietic stem-cell transplantation. However, the mechanisms involved in the mobilization of human hematopoietic stem and progenitor cells are largely unknown. To study the mobilization of human progenitor cells in an experimental animal model in response to different treatment regimens, we injected intravenously a total of 92 immunodeficient nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with various numbers of granulocyte colony-stimulating factor (G-CSF) -mobilized CD34+ PB cells (ranging from 2 to 50 × 106 cells per animal). Engraftment of human cells was detectable for up to 6.5 months after transplantation and, depending on the number of cells injected, reached as high as 96% in the bone marrow (BM), displaying an organ-specific maturation pattern of T- and B-lymphoid and myeloid cells. Among the different mobilization regimens tested, human clonogenic cells could be mobilized from the BM into the PB (P = .019) with a high or low dose of human G-CSF, alone or in combination with human stem-cell factor (SCF), with an average increase of 4.6-fold over control. Therefore, xenotransplantation of human cells in NOD/SCID mice will provide a basis to further study the mechanisms of mobilization and the biology of the mobilized primitive human hematopoietic cell.


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